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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (e.g. non GLP study, report finalized 5 years after study conduction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
as at 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
as at 1984,
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: in house breeding colony
- Age at study initiation: 6-10 (males) and 8-10 weeks (females)
- Weight at study initiation: 215-400 g (males) and 190 - 250 g (females)
- Fasting period before study: 16 h
- Housing: stainless steel cages with grating floor, 1 animal per cage
- Diet: standard diet ad libitum
- Water: ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 50 -65
- Photoperiod (hrs dark / hrs light): 6 a.m - 6 p.m. artificial lighting, 6 p.m.- 6 a.m. natural light dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 % (w/v)
- Amount of vehicle: 2.4, 3.0, 3.25, 3.75, 4.70 ml/kg bw


MAXIMUM DOSE VOLUME APPLIED: 470 mg/kg bw
Doses:
- 240, 300, 325, 375, 470 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: first 4 h after administration, then daily; Weighing: day 0 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy, histopathology of stomach and liver
Statistics:
- probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
315 mg/kg bw
95% CL:
303 - 357
Sex:
female
Dose descriptor:
LD50
Effect level:
356 mg/kg bw
95% CL:
317 - 426
Remarks on result:
other: error in calculation (report)
Sex:
female
Dose descriptor:
LD50
Effect level:
327 mg/kg bw
Remarks on result:
other: as recalculated by reviewer of the SIDS dossier on CAS 108-77-0
Sex:
male/female
Dose descriptor:
LD50
Effect level:
333.6 mg/kg bw
95% CL:
293.4 - 373.8
Remarks on result:
other: recalculated by the reviewer using the probit analysis using AnalystSoft, BioStat, statistische Analyse. Version 2008. (http://www.analystsoft.com/de/products/biostat/)
Mortality:
Mortality was observed between 24h post application and day 2
males: 240 mg/kg bw 0/5
300 mg/kg bw 0/5
325 mg/kg bw 4/5
375 mg/kg bw 5/5
470 mg/kg bw 5/5
females: 240 mg/kg bw 0/5
300 mg/kg bw 0/5
325 mg/kg bw 3/5
375 mg/kg bw 2/5
470 mg/kg bw 5/5
Clinical signs:
- hypokinesia, somnolency, decreased muscle tone, loss of righting reflex, loss of pain
reflex, loss of corneal reflex, piloerection, accelerated respiration and decreased body temperature
Body weight:
- no body weight determination on day 7
- all surviving animals showed body weight gain between day 0 and day 14
Gross pathology:
- Macroscopic findings noted at necropsy included: stomach lesions such as reddening, inflation,
reddened gastric mucous membrane, thickened fundus, fusion with peritoneum/liver/spleen and reddening
of the intestinal mucosa

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of this acute oral toxicity study a combined LD50 for both sexes of 333.6 mg/Kg bw (293.4 — 373.8 95% CL) was deduced in rats.